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Stevens-Johnson syndrome & toxic epidermal necrolysis
Stevens-Johnson syndrome & toxic epidermal necrolysis

Stevens-Johnson syndrome & toxic epidermal necrolysis

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous reactions characterised by extensive necrosis and detachment of the epidermis. They are primarily caused by adverse drug reactions as well as infections. SJS and TEN are both dermatological emergencies.

🔢 Classification

SJS and TEN are considered to be on the same spectrum of disease. The differentiating factor between them is the extent of total body surface area (TBSA) affected:

  • SJS - <10% TBSA involvement.
  • SJS/TEN overlap - 10% - 30% TBSA involvement.
  • TEN - >30% TBSA involvement.

💡 Erythema multiforme (EM) major has some overlap with SJS/TEN as they both have mucocutaneous involvement. EM involves inflammation and necrosis of the epidermis in characteristic targetoid lesions. SJS/TEN is more widespread and involves detachment of the epidermis with more severe epidermal necrosis.

Pathophysiology

The pathophysiology of SJS/TEN is not entirely understood but involves an abnormal immune response to drug metabolites or infection. Upon exposure to a an offensive agent, cytotoxic T cells and natural killer (NK) cells release proteins such as perforin, granzyme B, and granulysin. These proteins induce apoptosis in keratinocytes. These apoptotic keratinocytes release further pro-inflammatory cytokines such as TNF-alpha and IFN-gamma which further amplifies the immune response. This cascade results in extensive keratinocyte apoptosis and detachment of the epidermis from the dermis. This may present as epidermal necrosis and detachment. The epidermis is important in maintaining the skin barrier as well as retaining fluid, as such the skin loss that occurs with SJS/TEN leads to fluid loss, secondary infections and severe systemic complications such as septic shock and severe fluid losses.

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⚠️ Risk factors

As mentioned, SJS/TEN is commonly triggered by medications or infections. In rarer occasions, it may be due to other disease processes such as Graft-versus-Host disease (GvHD).

  • Medications
    • Antibiotics - sulfonamides, penicillins, rifampicin.
    • Corticosteroids
    • Antiretroviral drugs
    • Antiepileptic drugs - phenytoin, phenobarbital, lamotrigine, sodium valproate, carbamazepine, ethosuximide.
    • Oxicam NSAIDs - piroxicam.
    • Xanthine oxidase inhibitors - allopurinol
    • DMARDs - sulfasalazine.
  • Infections
    • Mycoplasma pneumoniae
    • Cytomegaloviruses
    • Herpes-simplex viruses
    • Epstein-Barr virus
    • HIV
    • Pharyngitis
    • Otitis media
  • Vaccinations - the smallpox vaccination, although rarely given, can precipitate erythema multiforme or SJS.
  • Graft-versus-Host disease (GvHD)
  • Autoimmune disease - such as SLE or rheumatoid arthritis.

😷 Presentation

As these conditions sit on a spectrum, some cases are mild others can be potentially fatal. Let’s take a look at some of the symptoms that may arise throughout the spectrum of disease:

  • Prodromal phase - this begins 1-3 weeks after taking the medication. Patients may develop non-specific symptoms such as:
    • Fever
    • Cough
    • Sore throat, mouth and eyes
    • Pruritis
  • Mucocutaneous lesions - this occurs 1-3 days after the onset of prodromal symptoms.
    • Purple or red rash - the rash spreads across the skin and begins to blister. It may have a targetoid appearance.
    • A few days after the blistering begins, the skin may then begin to shed, exposing the raw tissue underneath.
    • Mucous membranes may suffer from pain, blistering, shedding, erythema. This may happen on the lips too.
    • Eyes may become inflamed and ulcerated. This may occur in the urinary tract, lungs and internal organs.
  • Shock - due to severe volume losses or as a result of sepsis.

💡 Blisters may form when the skin is stroked or when mild lateral pressure is applied. This is known as a positive Nikolsky sign.

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🔍 Investigations

  • 🏆 Skin biopsy - this is the definitive diagnostic test. It will show keratinocyte necrosis/apoptosis with detachment of the epidermal from the dermis as well as sparse lymphocyte infiltration.
  • Skin swabs - to detect any skin infections that may have occurred.
  • CXR - to assess possible pneumonia or interstitial pneumonitis.
  • Blood tests
    • FBC
    • Blood cultures
    • CRP
    • Blood glucose
    • U&Es
    • LFTs
    • Mycoplasma serology
    • Coagulation studies - to assess for DIC.
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🧰 Management

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Management of Stevens-Johnson syndrome/toxic epidermal necrolysis:

As previously mentioned, they are medical emergencies and need admission to a dermatology or burns unit for treatment. TEN often requires ICU admission.

  1. Identify and stop the precipitating cause
  2. Supportive care - this includes nutritional care, analgesia, fluids and electrolyte corrections.

Treatment options include:

  • 🥇 IV immunoglobulin (IVIG) - commonly used first-line for TEN.
  • Immunomodulators - such as ciclosporin and cyclophosphamide.
  • Steroids - this is controversial and should be carefully weighed up as steroids suppress the immune system and as such it may lead to sepsis.
  • Plasmapheresis - may help remove immune complexes, pro-inflammatory cytokines and autoantibodies that contribute to the disease. It may also remove the precipitating factor (such as drug metabolites).

🚨 Complications

  • Secondary infection and sepsis
  • Permanent skin damage and scarring
  • Visual complications - this ranges from painful eyes to severe scarring and blindness.